Linked Life Data

15691506

Source:http://linkedlifedata.com/resource/pubmed/id/15691506

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-2-4
pubmed:abstractText
Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a newly found virus, called SARS coronavirus. In this study, the cleavage mechanism of the SARS coronavirus main proteinase (Mpro or 3CLpro) on the octapeptide NH2-AVLQ downward arrowSGFR-COOH was investigated using molecular mechanics and quantum mechanics simulations based on the experimental structure of the proteinase. It has been observed that the catalytic dyad (His-41/Cys-145) site between domains I and II attracts the pi electron density from the peptide bond Gln-Ser, increasing the positive charge on C(CO) of Gln and the negative charge on N(NH) of Ser, so as to weaken the Gln-Ser peptide bond. The catalytic functional group is the imidazole group of His-41 and the S in Cys-145. Ndelta1 on the imidazole ring plays the acid-base catalytic role. Based on the "distorted key theory" [K.C. Chou, Anal. Biochem. 233 (1996) 1-14], the possibility to convert the octapeptide to a competent inhibitor has been studied. It has been found that the chemical bond between Gln and Ser will become much stronger and no longer cleavable by the SARS enzyme after either changing the carbonyl group CO of Gln to CH2 or CF2 or changing the NH of Ser to CH2 or CF2. The octapeptide thus modified might become an effective inhibitor or a potential drug candidate against SARS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0003-2697
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
337
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
262-70
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase.
pubmed:affiliation
Tianjin Institute of Bioinformatics and Drug Discovery, Tianjin Normal University, Tianjin 300074, China. duqishi@yahoo.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't